Koumallos Nikolas, Antoniades Charalambos, Tousoulis Dimitris, Shirodaria Cheerag, Stefanadis Christodoulos
Athens University Medical School, A Cardiology Department, Athens, Greece.
Recent Pat Cardiovasc Drug Discov. 2006 Jun;1(2):185-91. doi: 10.2174/157489006777442487.
Heart failure is characterised by decreased cardiac output, which results in the development of both peripheral hypoperfusion and pulmonary congestion and can lead to the development of acute pulmonary edema. The primary objective in treating a patient with decompensated heart failure is hemodynamic stabilization, which is usually achieved by inotropic support. Classic inotropic agents provide short-term hemodynamic improvement, but their use has been correlated with poor prognosis. Levosimendan, a new calcium sensitizer, offers hemodynamic and symptomatic improvement without increasing cAMP and intracellular calcium concentrations. This agent improves contractility without increasing the risk of cardiac events such as arrhythmias. By combining a positive inotropic action mediated via calcium sensitization and a vasodilatory effect via ATP-dependent potassium channels, it appears to be superior than classic positive inotropic agents. Furthermore, it seems to have prolonged benefit in heart failure patients, and it also has anti-inflammatory and antiapoptotic properties. In conclusion, levosimendan seems to be a particularly promising agent for the treatment of decompensated heart failure, as in addition to improving cardiac output, it has a more favorable side-effect profile than classic inotropic agents, and it affects multiple pathways with key role in the pathophysiology of heart failure.
心力衰竭的特征是心输出量降低,这会导致外周灌注不足和肺充血,并可能引发急性肺水肿。治疗失代偿性心力衰竭患者的主要目标是血流动力学稳定,这通常通过使用正性肌力药物来实现。传统的正性肌力药物可提供短期的血流动力学改善,但它们的使用与不良预后相关。新型钙增敏剂左西孟旦可在不增加环磷酸腺苷(cAMP)和细胞内钙浓度的情况下改善血流动力学和症状。该药物可改善心肌收缩力,而不增加心律失常等心脏事件的风险。通过结合钙增敏介导的正性肌力作用和ATP依赖性钾通道介导的血管舒张作用,它似乎优于传统的正性肌力药物。此外,它似乎对心力衰竭患者有持久的益处,并且还具有抗炎和抗凋亡特性。总之,左西孟旦似乎是治疗失代偿性心力衰竭的一种特别有前景的药物,因为除了改善心输出量外,它比传统正性肌力药物具有更有利的副作用谱,并且它作用于心力衰竭病理生理学中起关键作用的多个途径。